Project Summary/ Abstract The inverse association between SES and health is well established. Its underlying causes are not. This application leverages and extends an active prospective longitudinal cohort of children and families in rural poverty to test key hypotheses about the ways in which early psychosocial and chemical exposures (0-5yrs) adversely affect pediatric health outcomes in the areas of neurodevelopment and obesity. We describe an ongoing population-based longitudinal study, the Family Life Project (FLP) with N=1292 children and their primary and when available, secondary caregivers, followed from birth and oversampled for poverty and African American ethnicity in predominantly low-income, non-urban counties in Pennsylvania and in North Carolina. Participants were seen at 8 time points birth to 5 years and at 6 time points 7 to 13 years. A primary focus of data collection and analysis has been the prospective investigation of associations between psychosocial early life stress and neurodevelopment in the areas of executive function, emotion regulation, tolerance for delay, language, school achievement, ADHD and LD. This application builds on and extends our prior data collection retrospectively and prospectively in order to amplify and enhance our focus on adverse exposures in relation to neurodevelopment and obesity risk. In the UG3 retrospective phase we expand our investigation of chemical and neighborhood level exposures when study children were 0 to 5yrs. In the UH3 prospective phase we propose data collection during two clinic visits when children are 16 and 18yrs. These visits will include the collection of all ECHO core elements plus biospecimens (blood, saliva, urine). With these data we will develop clearly defined neurodevelopment and obesity phenotypes and test our primary hypotheses linking early exposures to later health outcomes. We hypothesize direct effects of chemical and psychosocial exposures on our phenotypes as well as mediation of exposures through effects of allostatic load on the development of the central nervous system and the inflammatory processes of the immune system. Importantly, follow-up of the FLP sample into late adolescence will provide much needed information with which to reduce health disparities in high-risk, understudied rural populations. This follow-up will provide data to address key questions about the rural context and individual differences relating to race, gender, and geographic location that moderate relations between early exposures and later health outcomes. The FLP will make a unique and valued contribution to the ECHO synthetic cohort. Inclusion of the FLP will allow for the identification of factors that relate mechanistically to rural health outcomes and that can serve as the focus of prevention and intervention efforts.